Fig. 9

PrP driven overexpression of mutant or WT TDP-43 results in a dose-dependent impact on phenotype onset and survival. Data from all PrP-TDP-43 expression studies reported to date shows that overexpression of WT and/or mutant TDP-43 results in early phenotype onset and lethality when protein expression is approximately 2.3 fold or higher (dotted line) above endogenous. At expression levels lower than this, the mutant protein results in a non-lethal motor phenotype, while the WT protein does not induce a detectable phenotype. The data from our animals is consistent with this. For each mouse line, the first symbol represents onset, and the second represents survival. Circles represent WT lines, triangles represent mutant lines, and the squares represent the current compound transgenic line. Data from the current study is shown in blue, and numbers represent source reference